Journal of Materials Science and Nanomaterials
Open Access

Cell-adhesive nanopatterning shows tissue organization and intercellular communication network architecture are dynamically regulated by the underlying substrate information in mesenchymal condensation

Intercellular communication guarantees a continuous and efficient flow of biological information between cells and their surrounding
environment, which is essential to sustain homeostasis and function in living organisms.
Extracellular matrix (ECM) interactions are shown to regulate many biological processes such as cell shape, proliferation, migration,
differentiation and programmed cell death. Communication networks are known to be established during morphogenesis with a determining
contribution of the interactions with the ECM. Although some descriptive models on how cell membrane mechanochemical information propagates
from an initial random scenario to complex tissue patterning are available, a predictable model for ECM information propagation and the
establishment of a concurrent intercellular communication network is still lacking.
Hereby, we used substrates of tunable local surface adhesiveness to systematically control integrin-based cell-surface interactions during
mesenchymal condensation, a prevalent morphogenetic transition, for the study of ECM information propagation within tissue. Using chondrogenic
condensation as a model, we have conducted a systematic study on the influence of cell-matrix interactions in the establishment of an intercellular
communication network. We used previously developed dendrimer-based nanopatterns to control local cell-surface adhesiveness at the nanoscale.
We show that tuning of local adhesiveness enables control over the pre-cartilaginous condensation phase of mesenchymal cells. Cell condensates
of greater cohesiveness and stability are obtained on substrates where basal cells strongly interact with the surface, in accordance with an
integrin-based cohesion mechanism. More stable condensates also present increased connexin 43 (Cx43) expression and improved gap junction
intercellular communication (GJIC). Through a cell condensate transplantation assay, we show that both tissue organization and intercellular
communication architecture are dynamically regulated by the underlying substrate information that propagates in a continuous feedback mode.
The effect of substrate induces a rearrangement and adaptation of the cytoskeleton network of the basal cell layer, which propagates through the
condensate regulating membrane trafficking and the establishment of GJIC network.

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